Most women of reproductive age experience some physical or emotional disturbances in the days before menstruation. Symptoms are often mild, but 20–30% of women suffer from premenstrual syndrome (PMS), a moderate-to-severe cluster of symptoms, which impair daily activities during the luteal phase of the menstrual cycle and disappear at the onset of menstruation. The severe form of PMS, predominantly characterized by emotional and behavioral symptoms, is classified in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) as premenstrual dysphoric disorder (PMDD) and affects 3–8% of reproductive age women. PMS and PMDD are diagnosed through questionnaires in which women prospectively record symptoms and their severity during two menstrual cycles. The etiology of PMS and PMDD is complex, but the key feature is the altered sensitivity of the GABAergic central inhibitory system to allopregnanolone, a neurosteroid derived from the progesterone produced by the ovary after ovulation. Even the serotonergic system appears to be involved through reduced availability of serotonin. Thus, the therapeutic approach to PMS and PMDD targets both the hypothalamic–pituitary–ovarian axis and the brain neurotransmitter systems, and clinicians should consider each patient’s situation individually. Combined hormonal contraceptives (CHCs), which suppress ovulation, are the first choice in women who desire contraception, otherwise serotonin antidepressants should be the first-line treatment. Recent investigations concern modulation therapies for the GABAergic system, and promising results have been obtained with sepranolone. Other treatments for milder forms of PMS include lifestyle modifications, dietary supplements, and cognitive behavioral therapy (CBT).